The present invention relates to optically active intermediates, processes for preparing the optically active intermediates, and processes employing the optically active intermediates for preparing optically active substituted oximes, hydrazones and olefins useful as antagonists of tachykinin receptors, in particular as antagonists of the neuropeptides neurokinin-1 receptor (NK.sub.1) and/or neurokinin-2 receptor (NK.sub.2) and/or neurokinin-3 receptor (NK.sub.3).
Neurokinin receptors are found in the nervous system and the circulatory system and peripheral tissues of mammals, and therefore are involved in a variety of biological processes. Neurokinin receptor antagonists are consequently expected to be useful in the treatment or prevention of various mammalian disease states, for example asthma, cough, bronchospasm, inflammatory diseases such as arthritis, central nervous system conditions such as migraine and epilepsy, nociception, and various gastrointestinal disorders such as Crohn's disease.
In particular, NK.sub.1 receptors have been reported to be involved in microvascular leakage and mucus secretion, and NK.sub.2 receptors have been associated with smooth muscle contraction, making NK.sub.1 and NK.sub.2 receptor antagonists especially useful in the treatment and prevention of asthma. These NK.sub.1 and NK.sub.2 receptor antagonists are also useful in the treatment of cough, bronchospasm, inflammatory diseases such as arthritis, central nervous system conditions such as migraine and epilepsy, nociception, and various gastrointestinal disorders such as Crohn's disease.
Substituted oximes, hydrazones and olefins which may be made from the intermediates and processes of the present invention include the oximes, hydrazones and olefins described in International Application No. PCT/US 96/05659, filed on May 1, 1996, the contents of which are fully incorporated herein by reference. It is believed that these compounds exhibit greater activity as neurokinin antagonists when they are in the form of their R-enantiomers. Thus, it is desirable to have intermediates and processes that can be used to make such R-enantiomers. The present invention satisfies this objective.